A review of modern data on genetic knockout strategy application to study the brain neurotransmitters and their role in the regulation of behavior. Advantages and shortcomings of genetic knockout of receptors and the enzymes of neurotransmitters metabolism models in comparison to other methods are discussed. Data on the effect of genetic knockout of various types of opioid, dopamine, serotonin and adrenoreceptors as well as enzymes in biosynthesis of catecholamines and serotonin on physiology and behavior is adduced. The data provide evidence that genetic knockout reproduces a principal effects of the lack of receptors and enzymes and allows to find new yet unknown properties. Mouse strains with genetic knockout represent unique models of hereditary neuropathology. At the same time the data presented clearly demonstrated that the lack of a single type of receptor or enzyme does not lead usually to disorganization of regulated by them physiological functions and behavior. The data witness to the complexity and multifactoriality of their regulations and evidenced the great compensatory potentials of organism.
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Clin Transl Med
January 2025
Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: Sporadic aortic aneurysm and dissection (AAD) is a critical condition characterised by the progressive loss of vascular smooth muscle cells (VSMCs) and the breakdown of the extracellular matrix. However, the molecular mechanisms responsible for the phenotypic switch and loss of VSMCs in AAD are not fully understood.
Methods And Results: In this study, we employed a discovery-driven, unbiased approach.
Behav Brain Funct
December 2024
Department of Pharmacology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
The large-conductance calcium- and voltage-activated potassium (BK) channels, encoded by the KCNMA1 gene, play important roles in neuronal function. Mutations in KCNMA1 have been found in patients with various neurodevelopmental features, including intellectual disability, autism spectrum disorder (ASD), or attention deficit hyperactivity disorder (ADHD). Previous studies of KCNMA1 knockout mice have suggested altered activity patterns and behavioral flexibility, but it remained unclear whether these changes primarily affect immediate behavioral adaptation or longer-term learning processes.
View Article and Find Full Text PDFLab Anim Res
December 2024
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National Univ. Hospital, Seoul, Korea.
Background: Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan.
View Article and Find Full Text PDFBMC Infect Dis
December 2024
Shenzhen Third People's Hospital, National Clinical Research Centre for Infectious Disease, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
Background: Bacterial pathogens frequently encounter host-derived metabolites during their colonization and invasion processes, which can serve as nutrients, antimicrobial agents, or signaling molecules for the pathogens. The essential nutrient choline (Cho) is widely known to be utilized by a diverse range of bacteria and may undergo conversion into the disease-associated metabolite trimethylamine (TMA). However, the impact of choline metabolism on bacterial physiology and virulence remains largely unexplored.
View Article and Find Full Text PDFHum Cell
December 2024
Section of Oncopathology and Morphological Pathology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miazaki, 889-1692, Japan.
Hepatocyte growth factor activator inhibitor type 1 (HAI-1), which is encoded by the SPINT1 gene, is a membrane-associated serine proteinase inhibitor abundantly expressed in epithelial tissues. We had previously demonstrated that HAI-1 is critical for placental development, epidermal keratinization, and maintenance of keratinocyte morphology by regulating cognate proteases, matriptase and prostasin. After performing ultrastructural analysis of Spint1-deleted skin tissues, our results showed that Spint1-deleted epidermis exhibited partially disrupted epidermal basement-membrane structures.
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